The primary objective of the proposed project is to quantitate the probability of malignant transformation per surviving clonogenic cell per dose of carcinogen when hepatocytes are exposed to AAF, aflatoxin, and low LET radiation, and to determine whether this probability is cell cycle dependent. The project shall be divided into both short-term studies devoted to the development of a cell survival assay system and its application and long-term carcinogenesis experiments. The former will be accomplished by transplanting unexposed and carcinogen exposed monodispersed hepatocytes into the dorsal facia of isogeneic rats manipulated to provide an adequate stimulus for subsequent hepatocyte proliferation (e.g., partial hepatectomy). The chemical carcinogenesis studies entail in vitro exposure of enzymatically dispersed hepatocytes, transplantation of these cells into isogeneic rats and subsequent observation for tumor development. Similar studies will be performed with hepatocytes exposed to low LET radiation while in various stages of their cell cycle. By the use of these methods we hope to: 1) develop a system whereby the number of cells which survive an exposure to a carcinogen can be quantitated, 2) minimize the abscopal effects of chemical carcinogens and ionizing radiation, 3) develop a system where the probability of malignant transformation of hepatocytes exposed either in vitro or in vivo to either chemical carcinogens or radiation can be determined as a function of surviving clonogenic cells rather than total number of initially exposed cells, and 4) to ascertain whether the probability of malignant transformation is dependent upon cell cycle stage.